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Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors (RADIANT-3)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00510068
First received: July 31, 2007
Last updated: May 27, 2014
Last verified: May 2014

July 31, 2007
May 27, 2014
July 2007
February 2010   (final data collection date for primary outcome measure)
Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ] [ Designated as safety issue: No ]
Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
• Assess the clinical activity of everolimus plus best supportive care as defined by progression free survival, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in patients with advanced Neuroendocrine Tumors.
Complete list of historical versions of study NCT00510068 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response}) [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ] [ Designated as safety issue: No ]
    Objective Response defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of the longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks . Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) [ Time Frame: on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuation ] [ Designated as safety issue: Yes ]
    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
  • Time to Overall Survival [ Time Frame: Baseline, to death- no time limit ] [ Designated as safety issue: Yes ]
    Overall Survival Rate is the time from study start to death from any cause.
  • Evaluation of Pharmacokinetics (PK) Parameters [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ] [ Designated as safety issue: No ]
    The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameters were: area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last), area under the concentration time curve from time zero to time t, where t is the end of the dosing interval (AUC0-t), maximum (peak) drug concentration (Cmax), time to maximum (peak) drug concentration (tmax), and minimum (trough) drug concentration (Cmin).
  • Changes From Baseline in Serum Biochemical Tumor Markers, Such as Chromogranin A (CgA) and Neuron Specific Enolase (NSE) [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) ] [ Designated as safety issue: No ]
    Baseline levels of serum CgA and NSE were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated". NSE levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated".
To evaluate the effect of everolimus on other tumor endpoints: objective response rate (Complete Response [CR] and Partial Response [PR]), response duration To compare overall survival (OS) between the study arms
Not Provided
Not Provided
 
Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors
A Randomized Double-blind Phase III Study of RAD001 10 mg/d Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced Pancreatic Neuroendocrine Tumor (NET)

The purpose of this study was to evaluate progression free survival in those participants assigned everolimus 10 mg/day plus Best Supportive Care versus those assigned to placebo plus Best Supportive Care in Advanced Neuroendocrine Tumors

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Advanced Neuroendocrine Tumors
  • Drug: Everolimus
    A 10-mg dose of everolimus was given by continuous oral daily dosing of two 5-mg tablets.
    Other Name: RAD001
  • Drug: Placebo to Everolimus
    a 10-mg dose of matching placebo to Everolimus was given by continuous oral daily dosing of two 5-mg tablets.
  • Experimental: Everolimus 10 mg/day
    Participants received 10 mg per day of Everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
    Intervention: Drug: Everolimus
  • Placebo Comparator: Placebo
    Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
    Intervention: Drug: Placebo to Everolimus
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):514-23. doi: 10.1056/NEJMoa1009290.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
410
December 2017
February 2010   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. Patients must have advanced (unresectable or metastatic) biopsy-proven pancreatic NET
  2. Measurable disease by radiologic assessment
  3. Adequate blood work
  4. Performance Status 0-2 : Ability to be out of bed most of the time
  5. Adult male or female patients ≥ 18 years of age
  6. Women of childbearing potential must have a negative serum pregnancy test
  7. Written informed consent from patients must be obtained in accordance to local guidelines

Exclusion criteria:

  1. Patients with severe kind of (poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma) cancer are not eligible
  2. Other chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to starting this trial
  3. Hepatic artery procedure called embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation/ radiofrequency ablation of hepatic metastasis within 2 months of enrollment
  4. Prior therapy with the same kind of medication (mTOR inhibitors: sirolimus, temsirolimus, everolimus).
  5. Uncontrolled diabetes mellitus Patients who have any severe and/or uncontrolled medical conditions such as:
  6. Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
  7. Patients with a known history of HIV seropositivity
  8. No other prior or concurrent cancer at the time enrolling to this trial

Other protocol defined inclusion/ exclusion criteria applied

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Brazil,   Canada,   France,   Germany,   Greece,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Slovakia,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   United Kingdom
 
NCT00510068
CRAD001C2324, 2006-006819-75
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP